There have recently been proposed recombinant micro-organisms that have the capacity to produce certain stilbenoids of the general formula 1:
wherein each of R1, R2, R3, R4 and R5 independently is hydrogen or hydroxy. Examples of such compounds include resveratrol (only R3 being hydroxy) and pinosylvin (all of the R groups being hydrogen), see for instance WO2006/089898.
EP1181383 describes the in-situ extraction of a micro-organism fermentation product into an encapsulated organic solvent, the purpose being to prevent inhibition of production of the fermentation product caused by the product itself by sequestering it into the encapsulated solvent. This is therefore an approach to address the problem of a poor yield of the desired product.
U.S. Pat. No. 4,865,973 also tackles the problem of low metabolite yields due to product inhibition, this time by extraction of ethanol during cultivation of Saccaromyces cerevisiae yeast into a non-encapsulated solvent such as dodecylacetate.
US2004/0229326 again tackles the problem of product inhibition, this time in relation to aromatic compounds such as cinnamic acid, using a two phase extractive fermentation based on one or more of several defined solvents which include methyl decanoate.
Similarly, EP1715032 discloses a two phase fermentation using yeast to produce aroma compounds such as 2-phenylethanol with propylene glycol as extracting solvent to avoid product inhibition.
In fermentations to produce the stilbenoids with which the invention is concerned there is no problem relating to product inhibition however, as the existing strains of micro-organisms produce these compounds only in very small yields and it is not disclosed that they are secreted into the culture medium. Also, we have found that the solubility limit of the compounds is too low for product inhibition to become a problem.
Teachings such as WO2004/092344 describe biphasic reaction media for carrying out cell free enzymatic or other conversions, but this is of little relevance since there is no exposure of micro-organisms to the biphasic system.